KATP Antagonists for Preterm Infant Growth and Glucose Control

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Solution Overview

Problem

Preterm and low birth weight infants face challenges with hyperglycemia and impaired growth, and current insulin therapy methods, particularly intravenous administration, are risky and ineffective due to peripheral hyperinsulinemia and poor bioavailability of oral insulin formulations.

Innovation Solution

Enteral administration of a potassium ATP channel antagonist, such as glibenclamide, stimulates endogenous insulin secretion to treat hyperglycemia and promote catch-up growth in preterm and small-for-gestational-age infants, avoiding the adverse effects of insulin infusions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If intravenous insulin therapy is administered to preterm infants, then blood glucose control is improved, but the risk of hypoglycemia and mortality increases

Engineering Contradiction:
Improveblood glucose controlVSAvoidmortality risk
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

Instead of administering insulin directly (which causes peripheral hyperinsulinemia and hypoglycemia), the invention uses KATP channel antagonists to stimulate endogenous insulin secretion from pancreatic beta cells. This indirect approach through receptor antagonism reverses the conventional direct insulin administration strategy, achieving glucose control while avoiding the harmful effects of exogenous insulin.

Inventive Principle:
Principle #13The other way round (Inversion)

Solution Approach 2:

The KATP channel antagonist acts as an intermediary substance that mediates between the need for glucose control and the risk of hypoglycemia. By blocking KATP channels, it triggers endogenous insulin release in a controlled manner, serving as a mediator that achieves the desired metabolic effect without the direct risks of insulin therapy.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Ease of operation

If oral insulin formulations are administered to preterm infants, then the ease of administration is improved, but the bioavailability and effectiveness deteriorate

Engineering Contradiction:
Improveease of administrationVSAvoidbioavailability
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The invention changes the chemical parameter of the insulin delivery system by using KATP channel antagonists (sulfonylureas or meglitinides) instead of insulin itself. These compounds have oral bioavailability and are not degraded by digestive enzymes, fundamentally changing the delivery parameters to enable effective oral administration in preterm infants.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If KATP channel antagonist is administered enterally, then the safety is improved by avoiding hypoglycemia, but the device complexity increases

Engineering Contradiction:
ImprovesafetyVSAvoidtreatment complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The KATP channel antagonist enables the infant's own pancreatic beta cells to serve the function of insulin secretion. By stimulating endogenous insulin release, the body's own regulatory system serves itself, eliminating the need for complex external insulin delivery systems and monitoring required by conventional insulin therapy.

Inventive Principle:
Principle #25Self-service

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The method effectively manages hyperglycemia and supports growth in preterm infants by maintaining blood glucose levels and promoting growth without inducing hypoglycemia, offering a safer alternative to insulin therapy.

Implementation Method 1

Enteral administration of a potassium ATP channel antagonist, such as glibenclamide, stimulates endogenous insulin secretion

Methodology Applied
Scientific EffectATP-sensitive potassium channel antagonism:

Data Source

PatentEP2704716B1KATP antagonists (glibenglamid) for use for promoting growth of a premature infant
Publication Date: 2019.06.26 ASSISTANCE PUBLIQUE HOPITAUX DE PARIS (APHP)

AI summary

The present invention relates to pharmaceutical compositions comprising an ATP- sensitive potassium (K ATP) channel antagonist <e.g. sulfonylureas, meglitinides> and methods for treating hyperglycaemia and/or promoting growth a premature and/or small for gestational age infant.